Biomaterials made from polymers are being extensively applied in medicine and biotechnology, as well as in other industries. Applications include use as supporting materials, drug-delivery systems with different routes of administration and design, carriers of immobilized enzymes and cells, and materials for orthopedic applications.
Chitosan is a renewable biomaterial, β-[1→4]-2-amino-2-deoxy-D-glucopyranose, a functional and basic linear polysaccharide, and is prepared from chitin, the second most abundant biopolymer in nature. Chitosan is prepared by N-deacetylation of chitin, resulting in a copolymer of β-[1→4]-linked 2-acetamido-2-deoxy-D-glucopyranose and 2-amino-2-deoxy-D-glucopyranose. Chitosan is commercially available in a wide variety of molecular weight (e.g., 10-1000 kDa) and usually has a degree of deacetylation ranging between 70%-90%.
Recently there has been considerable interest in chitosan. For example, in U.S. Pat No. 5,645,844 to Henderson et, the inventor uses a negatively charged chitosan derivative delivery system which releases a semiochemical at a sustained rate over an extended period for time to attract a target insect to a selected location or to disrupt mating patterns. Watt et al., U.S. Pat. Nos. 6,465,626 and 6,391,318 uses chitosan in connection with vaccine compositions for intranasal administration. Cross-linked polymers of chitosan or alkoxy poly(alkylene oxide) conjugates of chitosan are described in U.S. Pat. No. 6,602,952 to Bentley et al. Crosslinking reactions with chitosan using sulfuric acid and glutaraldehyde are described in U.S. Pat. No. 6,228,291 to Lee et al.
Polymer emulsions comprising polymer particles having core-part and shell-part and having an average particle size of not more than 30 .mu.m, are disclosed in U.S. Pat. No. 6,359,032 to Kuwahara et al. The shell-part in Kuwahara is composed of chitosan and a polymer of an organic acid having a reactive vinyl group or a salt thereof as constituent components. The core-part is composed of a polymer of a hydrophobic monomer as constituent component or a mixture of the hydrophobic monomer and a non-polymerizable hydrophobic substance. U.S. Pat. No. 6,509,039 to Nies discloses a pharmaceutical composition comprising an active ingredient and a pharmaceutically acceptable carrier, where the carrier is a cross linked product of chitosan obtained by reacting chitosan with a carboxylic acid dianhydride or carboxylic acid polyanhydride. Compositions claimed to have pure nanoparticulate chitosan, which is free from surface modifiers or organic solvents are disclosed in U.S. Pat. No. 6,638,918 to Davison et al. The disclosures of the foregoing patents are hereby incorporated herein by reference.
The specific solubility characteristics of chitosan set limits to practical use. The only suitable aqueous media for dissolving chitosan are dilute acidic media such as hydrochloric acid, and some organic acids such as, for example, acetic acid and lactic acid. Chitosan is virtually insoluble in other media and conventional solvents. Chitosan solutions can be accordingly employed only where the aqueous acidic dissolving medium is not a problem. However, a variety of studies have focused on altering the water solubility of chitosan material in aqueous solution by employing water soluble linkages like phosphates, sulfates, cyanates and other agents.
Currently, because of its special set of properties, which include low or non-toxicity, biocompatibility, biodegradability, low immunogeneicity and antibacterial properties, chitosan has found wide application in a variety of areas, such as biomedicine, pharmaceutics, metal chelation, food additive, and other industrial utilizations.
Various methods have been developed for the crosslinking of chitosan including chemical modification of linear macromolecules with aldehydes, epoxides, cyanates and other agents, and ionically crosslinking reactions with charged ions or molecules to form bridges between polymeric chains. Crosslinking commonly results in gel formation.
Chitosan is of increasing interest in drug delivery. It is known, for example, to enhance transport of hydrophilic drugs. It has also reported to be useful in colon- or nasal delivery. Chitosan is also of current interest as a carrier in gene delivery. Several chitosan nanocomposites were evaluated based on the ionotropic gelation, or numerous chitosan/DNA nanoparticles were framed from the complexation of the cationic polymer with DNA plasmid. Ionically interaction and modification only of chitosan as cationic polymer and anions result in these particles.